Sarcopenia
Conditions
Keywords
microbiome, metabolome, aging, lean mass, physical function
Brief summary
The investigators recently published significant associations between circulating gut bacteria-related metabolites with lean and skeletal muscle mass and with measures of physical function in older adults, evidence that suggests a role for gut bacteria on the maintenance of these outcomes. To date, studies aimed at identification of associations between gut bacteria with lean mass or with specific measures of physical function have yet to be reported. Accordingly, the over-arching hypothesis is that gut bacteria are associated with, and are causatively involved in mechanisms that underlie the maintenance of lean mass and physical function in older adults. Results obtained from the proposed study are intended as the basis for future studies aimed at targeted modulation of the gut microflora, which may be a novel and innovative means for improving lean mass and physical function, and for addressing the public health priority of healthy aging in older adults.
Detailed description
In older adults (70+ years), reduced lean body mass and physical function are associated with increased disability, hospitalization, morbidity and mortality. Because older adults are the fastest growing global subpopulation, identification of mechanisms that underlie the maintenance of lean mass and physical function will be important for addressing the public health priority of healthy aging. Gut bacteria may be involved in mechanisms that underlie the maintenance of lean mass and physical function. In support of this hypothesis, in multiple publications the investigators recently reported significant associations between circulating gut bacteria-related metabolites with these outcomes in older adults. Accordingly, the overarching study hypothesis is that is gut bacteria are associated with, and are causatively involved in mechanisms that underlie the maintenance of lean mass and physical function in older adults. To test this hypothesis, the investigators propose to: characterize the association between fecal bacteria with lean mass and physical function (AIM 1), test the causative role of gut bacteria on the maintenance of lean mass and physical function by colonizing germ-free mice with fecal bacteria from older adults (AIM 2), and examine potential mechanisms that link gut bacteria with these outcomes by identifying associations between gut bacteria and serum metabolites with lean mass and physical function (AIM 3).
Interventions
None listed
Sponsors
Tufts University
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
70 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
i) Willing and able to sign the IRB approved informed consent form ii) Male and Female iii) 70-85 years of age iv) BMI ≤ 35 kg/m2 v) Willing to come to the HNRCA laboratory for baseline and 1-month follow-up study visits vi) SPPB ≥ 11 (High-Functioning, HF; 20 subjects: 10 males, 10 females) vii) 4 ≤ SPPB ≤ 7 (Low-Functioning, LF; 20 subjects: 10 males, 10 females)
Exclusion criteria
i) Non-English speaker ii) Acute or terminal illness iii) Surgery in the past 6 months iv) Lower extremity fracture within the past 6 months v) Myocardial infarction in the past 6 months vi) Coronary artery disease, peripheral vascular disease, previous stroke, or history of transient ischemic attacks vii) Cognitive impairment (MMSE score \< 23) viii) Uncontrolled hypertension (\> 160/100 mmHg) ix) Neuromuscular disease or drugs affecting neuromuscular function x) Androgen therapy in males xi) Estrogen therapy in females xii) Significant immune disorder xiii) Kidney Failure xiv) Pancreatic disease xv) Diabetes xvi) Gastrointestinal or malabsorption diseases xvii) History of cholecystectomy xviii) Use of probiotics, prebiotics or antibiotics in the past 3 months xix) The subject has any other condition, which in the opinion of the Investigator, precludes the subject's participation in the trial. xx) With the goal of matching the HF and LF groups for age, sex,and BMI, subjects may be excluded because their age, sex or BMI puts them outside the range needed for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Whole Body Lean Mass (%WBLM) | 1 month | %WBLM measured with dual x-ray absorptiometry (DXA). A higher %WBLM is indicative of a higher amount of whole-body lean mass, when compared with lower values. |
| Physical Function Measurement | 1-month | Short physical performance battery (SPPB) score. The SPPB is a combined measure of physical function that includes balance, a chair stand test (the time required to complete 5 chair stands), and the time needed to walk 4 meters. Each of these 3 tests are scored from 0 to 4. The scores for each individual test are summed, and accordingly, the lowest possible SPPB score would be 0, and the highest would be 12. A score of 12 would indicate good physical function, whereas a score of 0 is indicative of poor physical function. |
| 400-meter Gait Speed | 1-month | Measurement of 400-meter gait speed at the 1-month study visit compared against baseline. A slower time to walk 400 meters is indicative of worse physical function, when compared with a faster time. |
| Leg Press 1 Repetition Maximum | 1-month | Measurement of the leg press 1 repetition maximum at the 1-month study visit compared with baseline. The leg press 1 repetition maximum test involves the maximum amount of weight that the participant can push with their legs. A higher value is indicative of higher muscle strength, when compared with lower values. |
Countries
United States
Participant flow
Recruitment details
Recruitment dates: 5/2016 to 2/2018 at the Tufts University Human Nutrition Research Center on Aging (Boston, MA). Sedentary older adults were recruited from a database of older adults, and via advertisements posted on HNRCA bulletin boards and online media.
Pre-assignment details
Exclusion criteria included a SPPB score of 9 or 10, a BMI ≥ 35 kg/m2, acute or terminal illness, myocardial infarction in the past 6 months, unstable cardiovascular disease, MMSE score \< 23, blood pressure \> 150/90 mm Hg, androgen therapy in males, estrogen therapy in females, and others.
Participants by arm
| Arm | Count |
|---|---|
| High Functioning Defined by a short physical performance battery score (SPPB) greater than or equal to 11. | 18 |
| Low Functioning Defined by a short physical performance battery score (SPPB) less than or equal to 7. | 11 |
| Total | 29 |
Baseline characteristics
| Characteristic | Total | Low Functioning | High Functioning |
|---|---|---|---|
| 400-meter gait speed | 1.10 meters/second STANDARD_DEVIATION 0.18 | 0.96 meters/second STANDARD_DEVIATION 0.16 | 1.13 meters/second STANDARD_DEVIATION 0.16 |
| Age, Continuous | 76.3 years STANDARD_DEVIATION 3.79 | 77.0 years STANDARD_DEVIATION 4.43 | 75.9 years STANDARD_DEVIATION 3.42 |
| BMI | 28.0 kg/m^2 STANDARD_DEVIATION 3.6 | 27.6 kg/m^2 STANDARD_DEVIATION 3.7 | 28.7 kg/m^2 STANDARD_DEVIATION 3.5 |
| Leg press 1 repetition maximum value | 1699 Newtons STANDARD_DEVIATION 653 | 1407 Newtons STANDARD_DEVIATION 535 | 1878 Newtons STANDARD_DEVIATION 677 |
| Percentage of whole body lean mass | 65.7 Percentage of whole body mass STANDARD_DEVIATION 6.6 | 62.2 Percentage of whole body mass STANDARD_DEVIATION 6.4 | 67.3 Percentage of whole body mass STANDARD_DEVIATION 6.4 |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment United States | 29 participants | 11 participants | 18 participants |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 16 Participants | 6 Participants | 10 Participants |
| Short physical performance score (SPPB) | 10.1 scores on a scale STANDARD_DEVIATION 2.2 | 7.64 scores on a scale STANDARD_DEVIATION 1.29 | 11.5 scores on a scale STANDARD_DEVIATION 0.74 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 11 |
| other Total, other adverse events | 0 / 18 | 0 / 11 |
| serious Total, serious adverse events | 0 / 18 | 0 / 11 |
Outcome results
Primary
400-meter Gait Speed
Measurement of 400-meter gait speed at the 1-month study visit compared against baseline. A slower time to walk 400 meters is indicative of worse physical function, when compared with a faster time.
Time frame: 1-month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Functioning | 400-meter Gait Speed | 1.12 meters/second | Standard Error 0.16 |
| Low Functioning | 400-meter Gait Speed | 0.96 meters/second | Standard Error 0.19 |
Primary
Leg Press 1 Repetition Maximum
Measurement of the leg press 1 repetition maximum at the 1-month study visit compared with baseline. The leg press 1 repetition maximum test involves the maximum amount of weight that the participant can push with their legs. A higher value is indicative of higher muscle strength, when compared with lower values.
Time frame: 1-month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Functioning | Leg Press 1 Repetition Maximum | 1863.9 Newtons | Standard Deviation 665.1 |
| Low Functioning | Leg Press 1 Repetition Maximum | 1343.2 Newtons | Standard Deviation 565.3 |
Primary
Percentage of Whole Body Lean Mass (%WBLM)
%WBLM measured with dual x-ray absorptiometry (DXA). A higher %WBLM is indicative of a higher amount of whole-body lean mass, when compared with lower values.
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Functioning | Percentage of Whole Body Lean Mass (%WBLM) | 67.3 % of whole body mass | Standard Deviation 6.77 |
| Low Functioning | Percentage of Whole Body Lean Mass (%WBLM) | 61.9 % of whole body mass | Standard Deviation 6.64 |
Primary
Physical Function Measurement
Short physical performance battery (SPPB) score. The SPPB is a combined measure of physical function that includes balance, a chair stand test (the time required to complete 5 chair stands), and the time needed to walk 4 meters. Each of these 3 tests are scored from 0 to 4. The scores for each individual test are summed, and accordingly, the lowest possible SPPB score would be 0, and the highest would be 12. A score of 12 would indicate good physical function, whereas a score of 0 is indicative of poor physical function.
Time frame: 1-month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Functioning | Physical Function Measurement | 11.2 score | Standard Deviation 1.1 |
| Low Functioning | Physical Function Measurement | 7.4 score | Standard Deviation 1.5 |